Overactive Bladder (“OAB”) is a urological condition that affects approximately 50 million patients worldwide. A patient suffering from OAB typically experiences sudden yet frequent and unstoppable urges to urinate, even though the bladder may contain only a small amount of urine. This condition is usually associated with frequent and spontaneous contractions of the detrusor muscle, which is located in the bladder wall and surrounds the bladder.
The etiology of OAB is unclear, and indeed there may be multiple possible causes. OAB, however, is most often associated with detrusor muscle overactivity (i.e., frequent and spontaneous contractions of the detrusor muscle). These frequent contractions may fuse into a global and sustained contraction resulting in an urge to urinate. A malfunctioning detrusor muscle may cause overactive bladder. Indeed, there is a body of evidence suggesting that, in comparison with healthy bladders, overactive bladders exhibit localized changes in detrusor muscle morphology. These changes likely originate from defects on cellular and multi-cellular levels and changes in the nervous system. Such nervous system changes have been correlated to the observed local pathological changes in the muscle (e.g., patchy denervation, increased amount of connective tissue between muscle bundles), which may contribute to the abnormal function of the detrusor muscle.
Recent evidence suggests that the detrusor muscle may be triggered by substances released from the bladder wall when the wall experiences stimulation, such as stretching of the bladder wall. The released substances may include adenosine triphosphate (“ATP”), prostaglandins (“PG”), nitric oxide (“NO”), acetylcholine (“Ach”), and nerve growth factor (“NGF”). The release of these chemicals has been linked to over-expression of multiple receptors (muscarinic and cholinergic receptors, TRPV, etc.) and abnormally triggering the nerves (e.g., triggering increased bladder contractions in an OAB). Thus, there is a need to attenuate or block this communication. Targeting receptors with systemic drugs, however, may cause side effects, including adverse effects to other areas of the body carrying those receptors. For example, in addition to the urinary tract, muscarinic receptors and other types of receptors reside in other organs such as the heart, salivary glands, gastrointestinal tract, eyes, heart, and brain.